Vitamin D - additional info

It is well known that Vitamin D now has anti-inflammatory effects on the heart and kidneys. But so do some drugs. As I have spoke before, the family of blood pressure medications known as ACE inhibitors and ARBs are also inflammatory. Both of these family of medications attempt to suppress a hormone in the body called Angiotension II. What is angiotension? It is part of the RAAS system which attempts to maintain blood pressure when dehydration or low blood pressures occur. (Read my previous entry on the RAAS system). This occurs through the chloride sensing systems of the kidneys. When chloride delivery to the kidneys drop then certain cells (called the Macula Densa) produce a hormone called renin which later leads to the conversion of Angiotensin to Angiotensin II.


Angiontensin II has the following effects:

• Vasculature: vasoconstriction (constricting the vessels resulting in higher blood pressures)


• Neuro: it increases the sensation for salt and thirst. It also increases the secretion of ADH (from the posterior pituitary gland) which tells the kidneys to retain water. Also ACTH is released from the anterior pituitary gland which signals the adrenal glands to produce cortisol.


• Adrenal glands: increased production of aldosterone which signals the kidneys to retain sodium and excrete potassium into the urinary system.


• Kidneys: causes sodium retention causing blood pressure to go up.

Angiotensin II also: (1)

• increases pressure within the kidneys


• increases fibrosis (scarring)


• increases the recruitment of pro-inflammatory white blood cells


• increases the production of inflammatory cytokines (chemicals)


• increases cell proliferation

Essentially Angiotensin II is a proinflammatory hormone when consistently elevated. Vitamin D inhibits the activity of renin - thus leading to less Angiotension II production. Moreover, Vitamin D inhibits one of the master proteins for inflammation in the body called NF-kB which I have spoke about on many occasions. (click here) NF-kb is responsible for promoting gene signals to promote cellular:

• survival; meaning preventing cellular death (apoptosis)
  proliferation


• angiogenesis (development of more vasculature to increase blood flow)
  transformation (changing from one cell type to another)


• inflammation


• migration of cells


• invasion (meaning that the immune system can move to a specific site and then enter the tissue)

1) Min, L, Batuman, V: Vitamin D: a new hope for chronic kidney disease. Kidney International. 2009, 76(2); 1219-1221; commentary

Coconut and Red Wine

Coconut Oil

I get a lot of my patients telling me that Coconut Oil (saturated fat) is a detrimental form of fat to consume. I came upon a study in HUMANS that relays a different story. The 12 week study (1) was performed on Brazilian women with abdominal obesity. The randomised, double-blind, clinical trial involved 40 women aged 20-40 years. There were two groups:

• 30ml of soybean oil (polyunsaturated omega 6)


• 30ml of coconut oil (saturated fat)

The coconut oil group had a:

• higher level of HDL (48.7 +/- 2.4 vs. 45.00 +/- 5.6)


• lower LDL:HDL ratio (2.41 +/- 0.8 vs. 3.1 +/- 0.8; P = 0.04).


• reductions in BMI were observed in both groups, but only the coconut group exhibited a reduction in waist circumference

The soybean group showed an increase in:

• total cholesterol


• LDL


• LDL:HDL ratio


• but lower HDL

Red Wine

Red wine is known for its antioxidants called polyphenols. A recent study (2) has revealed that the flavanoids in red wine (such as delphinidin) exert their effects by stimulating the Estrogen Receptor Alpha on endothelial cells of vessels. Stimulation of the Estrogen Receptor Alpha increases Nitric Oxide (NO) levels leading to vasodilitation. Resveratrol is another polyphenol in red wine but is not a flavanoid. See Wikipedia about flavanoids.

NO is important to vascular health as it:

• inhibits PAI-1 (which promotes clotting)


• inhibits VCAM (vascular cell adhesion molecules) as well as ICAM which are used in inflammatory settings to recruit WBCs. This is a mechanism of coronary artery disease.
• inhibits platelet aggregation
• causes vasodilitation (dilates the vessel)

1) Assunção ML, Ferreira HS, dos Santos AF, Cabral CR Jr, Florêncio TM: Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity. Lipids. 2009 Jul;44(7):593-601.

2) Chalopin M, Tesse A, Martínez MC, Rognan D, Arnal J-F, et al. (2010) Estrogen Receptor Alpha as a Key Target of Red Wine Polyphenols Action on the Endothelium. PLoS ONE 5(1): e8554.

Alzheimer's Disease

Alzheimer's Disease affects 50% of the population over the age of 85%! (1) The mechanism of such a disease is not fully understood. However, the basic cause of Alzheimer's Disease is the deposition of proteins called beta amyloid proteins in the brain. It has been shown that Vitamin D increases the clearance of such proteins. (2) This works by Vitamin D increasing the activity of Type I macrophages in clearing beta-amyloid proteins. (2) Furthermore, the addition of curcuminoids (curcumin like antioxidants, Curry) with Vitamin D enhanced beta amyloid clearance. Also, midlife coffee consumption decreases the risk of Alzheimer's Disease by up to 65% with 3-5 cups per day. (3) Like Vitamin D, blueberries also increase the clearance of beta amyloid. (4)Strangely, diabetes slows the cognitive decline of Alzheimer's Disease. (5)


There is a high association of Alzheimer's and the lipoprotein Epo E - especially the EpoE4 variant. From Wikipedia (click), these are the subtypes of ApoE:

• E2 is associated with the genetic disorder type III hyperlipoproteinemia and with both increased and decreased risk for atherosclerosis.


• E3 is found in approximately 64 percent of the population. It is considered the "neutral" Apo E genotype.


• E4 has been implicated in atherosclerosis and Alzheimer's disease

The Epo E lipoprotein is responsible for the catabolism of triglyceride rich lipoproteins and is produced in the astrocytes of the brain. Astrocytes are responsible for: (source Wikipedia)

• biochemical support of endothelial cells which form the blood-brain barrier


• provision of nutrients to the nervous tissue


• maintenance of extracellular ion balance


• and a principal role in the repair and scarring process of the brain and spinal cord following traumatic injuries

About 60–80% of Alzheimer's patients have at least one copy of apoE4. (1) EpoE in mostly internalized into cells by the LDL Receptor (LDLR). A recent study in PLOS One (1) has shown that beta amyloid interferes with cellular uptake of LDL in the brain. The process is as follows. LDLR is normally found on the cell surface. It is created in an organelle in the cell called the Golgi Apparatus. LDLR is then shuttled to the cell surface for stimulation by LDL lipoprotein. LDL docks with the LDLR and then is incorporated within the cell.

Intracellular microtubules allow for shuttling of LDLR to the cell surface. Less LDLR at the cellular surface entails less intracellular cholesterol. As a result, the cell senses a low intracellular cholesterol level and produces more LDLR – worsening the situation. (see cartoon) Over expression of beta amyloid and amyloid precursor protein (APP) can cause such a scenario according to the study in PLOS One (1). Another recent study found that over expression of the LDLR increases the clearance of beta amyloid. (13)

Calorie restriction (6) and caffeine (7) lowers the amount of deposition of beta amyloid in mice. Mild cholesterol depletion reduces beta amyloid production. (8) Furthermore aluminum has been demonstrated in amyloid fibers in patients with Alzheimer's Disease. (9) The Angiotensin II Receptor Blocker (ARB), olmesartan improved cognitive function in Alzheimer's Disease patients. (10)

Therefore, all above data asks the question – Is Alzheimer's Disease an illness of increased beta-amyloid deposition or decreased beta amyloid clearance? Considering that Vitamin D increases the clearance of beta amyloid, maybe genetic variants of the Vitamin D Receptor (VDR) may play a role?

A Turkish study in 2007 looked at this exact situation.(11) The authors found that the Aa genotype for the VDR had a 2.3 times higher risk of Alzheimer's Disease than the AA gennotype. The AT haplotype was higher in the control group indicating a possible protective role for this haplotype against Alzheimer's Disease. (click here for the full article)

In another study in November, 2009 (12) the authors looked at the variants of the enzyme Hydroxyvitamin D3 1-alpha-hydroxylase. This enzyme is coded by the CYP27B1 gene. A genetic variation in the CYP27B1 gene lead to an increased risked of heart failure. Hydroxyvitamin D3 1-alpha hydroxylase is responsible for the conversion of 25-OH Vitamin D (inactive Vitamin D) to 1,25 OH Vitamin D (active form) in the kidneys.

All of this makes me wonder how important variants in Vitamin D expression must have been for the evolution of man. Especially taking in consideration that northern migration from Africa meant lighter skin tones for enhanced Vitamin D production and survival. I have always wondered if Vitamin D also plays such a vital role in other animal species other than humans. Or is it that a deviation from our other primate cousins in terms of diet lead for Vitamin D to be critically important for humans. Bigger brains and a higher capacity of intelligence required more calorie-dense food choices. Studies have shown that Vitamin D deficiency is associated with low mood and worse cognitive performance. (14,15)

1) Abisambra JF, Fiorelli T, Padmanabhan J, Neame P, Wefes I, et al. (2010) LDLR Expression and Localization Are Altered in Mouse and Human Cell Culture Models of Alzheimer's Disease. PLoS ONE 5(1): e8556. doi:10.1371/journal.pone.0008556

2) Masoumi A, Goldenson B, Ghirmai S, Avagyan H, Zaghi J, Abel K, Zheng X, Espinosa-Jeffrey A, Mahanian M, Liu PT, Hewison M, Mizwickie M, Cashman J, Fiala M: 1alpha,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer's disease patients. J Alzheimers Dis. 2009 Jul;17(3):703-17.

3) Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M: Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. J Alzheimers Dis. 2009 Jan;16(1):85-91.

4) Zhu Y, Bickford PC, Sanberg P, Giunta B, Tan J: Blueberry opposes beta-amyloid peptide-induced microglial activation via inhibition of p44/42 mitogen-activation protein kinase. Rejuvenation Res. 2008 Oct;11(5):891-901.

5) Sanz, C, et al: Diabetes is associated with a slower rate of cognitive decline in Alzheimer disease. Neurology. 2009 Oct 27;73(17):1359-66.

6) Mouton PR, Chachich ME, Quigley C, Spangler E, Ingram DK: Caloric restriction attenuates amyloid deposition in middle-aged dtg APP/PS1 mice. Neurosci Lett. 2009 Oct 30;464(3):184-7. Epub 2009 Aug 20.

7) Arendash GW, Schleif W, Rezai-Zadeh K, Jackson EK, Zacharia LC, Cracchiolo JR, Shippy D, Tan J: Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain beta-amyloid production. Neuroscience. 2006 Nov 3;142(4):941-52.

8) Guardia-Laguarta C, Coma M, Pera M, Clarimón J, Sereno L, Agulló JM, Molina-Porcel L, Gallardo E, Deng A, Berezovska O, Hyman BT, Blesa R, Gómez-Isla T, Lleó A: Mild cholesterol depletion reduces amyloid-beta production by impairing APP trafficking to the cell surface.
J Neurochem. 2009 Jul;110(1):220-30.

9) Yumoto, S, et al: Demonstration of aluminum in amyloid fibers in the cores of senile plaques in the brains of patients with Alzheimer's disease. J. Inorg Biochem. vol 103 (11); 1579-84.

10) Takeda S, Sato N, Takeuchi D, Kurinami H, Shinohara M, Niisato K, Kano M, Ogihara T, Rakugi H, Morishita R: Angiotensin receptor blocker prevented beta-amyloid-induced cognitive impairment associated with recovery of neurovascular coupling. Hypertension. 2009 Dec;54(6):1345-52

11) Gezen-Ak D, Dursun E, Ertan T, Hanağasi H, Gürvit H, Emre M, Eker E, Oztürk M, Engin F, Yilmazer S: Association between vitamin D receptor gene polymorphism and Alzheimer's disease. Tohoku J Exp Med. 2007 Jul;212(3):275-82.

12) Wilke RA, Simpson RU, Mukesh BN, Bhupathi SV, Dart RA, Ghebranious NR, McCarty CA: Genetic variation in CYP27B1 is associated with congestive heart failure in patients with hypertension. Pharmacogenomics. 2009 Nov;10(11):1789-97.

13) Kim J, Castellano JM, Jiang H, Basak JM, Parsadanian M, Pham V, Mason SM, Paul SM, Holtzman DM. Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance. Neuron. 2009 Dec 10;64(5):632-44.

14) Wilkins CH, Sheline YI, Roe CM, Birge SJ, Morris JC: Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry. 2006 Dec;14(12):1032-40.

15) Wilkins CH, Birge SJ, Sheline YI, Morris JC: Vitamin D deficiency is associated with worse cognitive performance and lower bone density in older African Americans. J Natl Med Assoc. 2009 Apr;101(4):349-54.

The Brain, Bone, and Metabolism

Although medical science is very advanced, only a small portion of the brain's full functions are known. Moreover, the brain itself has different sub-divisions: 1) the cortex which is involved in higher thinking and 2) the lower brain which is involved in more primitive functions like hunger and satiety (fullness). In fact, the area of the brain a that controls the hunger/satiety sensations is the hypothalamus - specifically within the arcuate nucleus of the hypothalamus.

There are two collections of neurons in the arcuate nucleus:

• NPY/AGRP - which signals a state of hunger - also referred to as orexingenic signals.


• POMC - which signals a state of fullness (satiety) - also referred to as anorexigenic signals

There are several hormones in the body which stimulate these neurons for hunger and satiety:

• leptin - is an adipose hormone which causes satiety by stimulating the POMC neurons and inhibiting the NPY/AGRP neurons. In the metabolic syndrome there is leptin resistance on the hypothalamus.


• ghrelin - is a hormone from the stomach that stimulates hunger through NPY/AGRP.


• peptide tyrosine-tyrosine (PYY) - produced from the GI tract causing satiety. It is released with the ingestion of food. PYY causes a slowing of the intestines and decrease gallbladder contractions.


• glucagon-like peptide-1 (GLP-1) - produced from the intestines and causes satiety as well as slowing down gastric emptying. GLP-1 also increases insulin and decreases glucagon production. A new drug for diabetes called stigagliptin (Januvia) inhibits the enzyme that breaks down GLP-1 thereby increasing insulin levels.


• oxyntomodulin (OXM) - produced in the GI tract and causes satiety.


• Resistin - an adipose hormone that causes insulin resistance. Resistin stimulates NPY/AGRP causing hunger. Resistin also increases TNF-alpha and IL-6 levels which: (2)

1. inhibit the actions of leptin and insulin on the hypothalamus.
2. causes cachexia (severe weight loss) as seen with cancers and infections.
3. reduce lipid accumulation
4. increase fatty acid break down (lipolysis) in adipose tissue

Therefore, with leptin and insulin resistance and elevated levels of TNF-alpha and IL-6, fatty acids will be stored less in the adipose tissue. There will be an increase of serum lipids that will be able to be stored in non-adipose tissues. Thus intact leptin is important in maintaining lipid storage in the adipose tissue and not accumulating in non-adipose tissues that were not designed for triglyceride storage (i.e. vascular disease -strokes, coronary artery disease, peripheral vascular disease). Omega 3 fatty acids reduce levels of TNF-alpha and IL-6 and thus lower serum triglyceride levels.

If that was the full story, I would be impressed. However, it gets much better. A new study reveals that NPY(neuropeptide Y) also influences Bone Density as well. Scientists from Australia have discovered that NPY decreases bone mass whereas a lack of NPY expression increased bone mass through increased osteoblast activity. Osteoblasts are the cells in the bone which create bony material. Osteoclasts break down the bony structure.

What does this mean? Since NPY is a signal of hunger, during states of fasting, there would be less bone growth so that more minerals could be used for other cellular processes in the body. But on the other hand, in states of fullness and inhibition of NPY, bone mass would increase. Why? For a simple reason. More bone mass would be required in order to support greater fatty tissue (meaning weight). This goes back to a an evolutionary scenario. During the summer, ancient man eat more (like carbs) and gained weight. NPY was suppressed and bone density was increased to support the newly gained weight. Whereas, in the winter during decreased calorie intake, less minerals and proteins were used for bone structures in order to allow for more usage else where in the body. It was a matter of survival.

At the end of the article, the authors pointed out that this hypothalamic-bone relationship is only a partial mechanim. NPY is also locally expressed in the bone itself. It is believed that weight bearing activity would locally, in the bone, decrease NPY activity allowing for more bone growth. Sounds familiar? Weight bearing exercises are good for healthy bone structure. Moreover, astronauts, which lack weight bearing activity, are more prone to bone loss. The authors believe that this hypothalamic-bone relationship fine tunes the already local bone NPY activity.

In summary, the brain (hypothalamus) senses energy status in the body. With impending weight gain, the brain signals the bone to prepare for greater loads and stress. With starvation, energy conservation is critical, allowing for more nutrients to be available for critical organs like the heart, brain, and the AMAZING kidneys. (Sorry for the bias. It is in my training)

In terms of the Summer/Winter modes, let's take it one step further. During the summer, there was a higher fructose consumption (fruit trees) which lead to weight gain. What does growing bones need? Vitamin D! Summer was the peak of Vitamin D production through the skin. NPY would go down and weight gain, bony mass, and Vitamin D would go up. Moreover, as recently stated, Vitamin D has insulin sensitizing effects as it is associated with higher adiponectin levels. Higher fructose loads means higher triglyceride levels. Adiponectin would counteract the possibility of the metabolic syndrome to an extent. However, the carb load is so high in the Western Diet that one can "forget about it!" (in New York-Italian accent)

1) Baldock PA, Lee NJ, Driessler F, Lin S, Allison S, Stehrer B, Lin EJ, Zhang L, Enriquez RF, Wong IP, McDonald MM, During M, Pierroz DD, Slack K, Shi YC, Yulyaningsih E, Aljanova A, Little DG, Ferrari SL, Sainsbury A, Eisman JA, Herzog H: Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight. PLoS One. 2009 Dec 22;4(12):e8415

2) Ahima, R: Brain regulation of appetite and satiety. Endo and Met Clinics of North Amer. 2008 Dec;37(4):811-23.

Vitamin K2 - a summary

I came upon a great review article the other day on Vitamin K2. The article can be down loaded here:

Vitamin K2: Monograph
Altern Med Rev. 2009 Sep;14(3):284-93.

My original article of Vitamin K2 is here.


Here is a brief summary of the article.

Vitamin K1 (common Vitamin K) is in the family referred to as phylloquinones.

Vitamin K2 is in the menaquinone family. One often sees Vitamin K2 referred to as MK-4 and MK-7. MK7 is longer acting but not necessarily more optimal. MK-4 is the form found in organ meats.

Those who are prone to Vitamin K deficiency are ones who:

• are on certain anti-coagulants
• have fat malabsorption states like biliary cirrhosis
• repeat usage of antibiotics. Certain bacteria in the GI tract produce Vitamin K.

Bone
The role of Vitamin K2 in the bone is to convert Glutamic Acid Residues (GLA) to Gamma-Carboxyglutamic Acid Residues (GLU). Such a conversion allows for calcium incorporation into the bones by such bone supporting proteins like osteocalcin.

Osteoporosis
Here is some studies:

1) In a 2 year study, 241 osteoporotic women were placed in two groups: A) K2 45mg/day with 150 mg calcium or B) 150mg of calcium. The fracture risk rate was significantly better in group A vs B (10% vs 30%).

2) In a 24 week study, 80 osteoporotic patients: A) K2 90mg/day vs B) placebo. The results for the second metacarpal Bone Mineral Density (BMD) was: Group A: an increase by 2.20 +/- 2.48% vs Group B: decrease by 7.31 +/- 3.65% This is impressive for only a 24 week study.

3) In a 1 year study, 172 osteoporotic/osteopenic women in groups: A) K2 45mg/day with 1,25OH Vitamin D3 1mcg/day vs B) K2 alone. BMD results: Group A (combination) - increase by 4.92 +/- 7.89% vs Group B 0.135 +/- 5.44 %

4) Steroids like prednisolones can cause drug induced osteoporosis. In a 8 week study, 60 patients of oral steroids for immune induced kidney disease were randomized to: A) 1,25OH Vit D3 0.5mcg/day; B) K2 45mg/day; C) D3 + K2 ; D) placebo. The BMD was: D) placebo - decreased by 3.19 +/- 1.11%; A) Vitamin D - maintained BMD + 0.28 +/- 1.30; B) K2 - maintained BMD + 0.50 +/- 1.17; and C) K2 + D3 maintained BMD +0.44 +/- 1.36

Cancer
Vitamin K2 has anti-cancerous effects on cancers of the:

• liver
• colon
• stomach
• lung
• leukemia
• lymphocyte
• nasopharnyx
• breast
• oral epidermoid

Cardiovascular Health

Vitamin K2 has inhibitory effects on vascular calcifications.

refer to my previous post about this topic

Vitamin Interactions

In the medical journal JAMA, 2007 (click here), an article was published showing that Vitamin A and E supplementation increased the risk of mortality. In an Israeli study (Dec 2009), the authors noted that in 300,000 subjects, Vitamin E supplementation served no benefit. Why do I bring this up? At the end of the Vitamin K2 article, the author notes two studies which showed that Vitamin E doses above 800 IU can antagonize the effects of Vitamin K. This can increase the risk of bleeding in patients on anticoagulant therapy or already Vitamin K deficient. Moreover, high dose Vitamin A can interfere with Vitamin K absorption. Which brings up the question whether the decreased availability of Vitamin K is a mechanism of action for the two above studies mentioned.

NOTE: Patients on anti-coagulants like Coumadin should not take Vitamin K supplements as this will antagonize the drug.

Vitamin D and the Kidney

Happy New Year to all! To start the New Year, I want to talk about an interesting observation that I have been noticing in the office. Vitamin D has been actually improving the kidney function of some of my patients with chronic kidney disease. I have a 68 year old Afro-American, diabetic female patient who I have been prepping for initiation of dialysis. Here creatinine was 4.8 mg/dL (translation - around 18% kidney function). With a Vitamin D level of 52 ng/ml, her creatinine came down to 3.6 mg/dL (translation - this gave her another 5-6% kidney function). It goes farther than just kidney function itself but also the amount of protein spillage in the urine called proteinuria also seems to be decreasing in some patients.



The question is how does Vitamin D protect the kidneys? In order to answer this, a short description of renal physiology is in order. The outer perimeter of the kidney has a filtering area called the glomerulus. Microscopically, the kidney filter contains many proteins which allow the transition of water, electrolytes, and waste products through the filter - but NOT proteins like albumin. Diabetes and Lupus cause the filter to become "leaky" allowing for various proteins to get through the kidney filter like: (1)

• albumin
• Vitamin D Binding Protein
• iron, copper, zinc binding proteins
• anti-clotting proteins
• thyroid hormone binding proteins
• immunoglobulins
• and may others

The basic structure of the filtering system is seen in the cartoon above. The elements of the blood (like sodium) are filtered from the capillary side of the kidney, through the filtering system, and into the urinary side of the kidney. Elements have to go through the Glomerular Basement Membrane (GBM) and then on to the Podocytes. The Podocytes severe as structural support as well as part of the filtering system. Between the podocytes, there is a membrane called the Slit Diaphragm which consists of a protein called Nephrin. The podocytes also contain proteins called Podocin.

Vitamin D increases the expression of both Nephrin and Podocin. (2) Thus, the barrier of the filtering system is strengthened from leaking proteins. In return, this brings up the question - "Who cares if some protein leaks through the kidney filter? It is a natural element that the body produced itself." The answer is that heavy amounts of protein filtering through the kidneys (such as greater than 3000 mg/ 24 hours) can microscopically scar the kidney itself leading to failure over time.

This is one explanation of how Vitamin D protects the kidneys. Another is that Vitamin D decreases the expression of the kidney hormone called renin. As discussed before (click here) renin is part of the Aldosterone-Renin-Angiotension System (RAAS) which allows for sodium conversation and increases blood pressure. Moreover, aldosterone has fibrotic effects - i.e. like on the cardiac tissue. Therefore, drugs that block the RAAS system (like ACE-inhibitors and ARBs) are not only blood pressure lowering drugs but also anti-inflammatory drugs. The concept of Vitamin D lowering blood pressure itself is controversial. (If you did not understand this paragragh then please review the previous entry on the RAAS system.)

The final mechanism of Vitamin D is that it inhibits the activity of the inflammatory proteins TNF-alpha and NF-kB. Recall that much of modern human disease is based on one simple concept - INFLAMMATION. Inhibiting Renin, TNF-alpha, and NF-kB are mechanisms of how Vitamin D would actually protect cardiac and vascular tissues. Amazing!

The scary issue that SICK patients are admitted to the hospital and are receiving NO direct sunlight. Most patients in the hospital setting are also receiving no or little Vitamin D supplementation (aside from a little dairy). As time progresses in the hospital, the Vitamin D levels further decrease - thus worsening an already bad situation. What I have been doing is empirically placing patients on Vitamin D and simultaneously checking their Vitamin D levels. The dilemma - it may take several days to over a week to get the actual Vitamin D level back. Can more lives be saved in the hospital setting with the administration of Hormone D? I think so.

How else dose Vitamin D protect the kidney and vascular system? Inflammation occurs by the increased activity of the inflammatory cytokine (chemical ) TNF-alpha which later stimulates the inflammatory protein called NF-kB. This leads to the increased expression of another protein called RANTES. RANTES increases the recruitment of white blood cells (WBCs) like T-cells, eosinophils, basophils, and leukocytes. (click here for more info) This is the initial mechanism of coronary artery disease and other vascular disease. Vitamin D inhibits the activity of both NF-kB and RANTES. Thus it prevents inflammation and the recruitment of other WBCs which would further increase the state of inflammation.

On a final note, another study from Thailand has shown a positive correlation between Vitamin D and adiponectin levels in diabetics. Adiponectin is the fat hormone which sensitizes Insulin. Thus higher adiponectin levels would translate to better diabetic control. (click here)

Quote from the abstract:

"High prevalence of vitamin D inadequacy and seasonal variation of vitamin D status are found in Thai population. We demonstrated an association between insufficient vitamin D status and lower circulating adiponectin in subjects with abnormal glucose tolerance independently of adiposity which may indicate the role of adiponectin as a link between vitamin D status and insulin resistance."

It appears that Vitamin D carries many roles going way beyond just bone health. The government needs to get with the program. They may be able to save millions of dollars with better recommendations about a "simple Vitamin."

1) Orth, SR, Ritz, E: The Nephrotic Syndrome. NEJM. 1998 Apr 23;338(17):1202-11

2) Doorenbos CR, van den Born J, Navis G, de Borst MH. Possible renoprotection by vitamin D in chronic renal disease: beyond mineral metabolism. Nat Rev Nephrol. 2009 Dec;5(12):691-700.

Evolutionary Medical Care

My take on EVOLUTIONARY MEDICAL CARE

This is my approach to evolutionary medical care. First, it must be a team effort. Second, the patient must be the primary team member. After all, who knows you better than you yourself? A doctor who is not like minded, can not successfully guide and monitor you in your recovery from diseases of the metabolic syndrome and obesity. Beside you and for safety, your team should consist of a primary doctor (a physician who is responsible for your health care) along with all specialties that cover your specific metabolic syndrome diseases. The primary doctor must be evolutionary lifestyle oriented, and practice evolutionary medicine, in effect, a high saturated fat and a low carbohydrate eating plan is optimal. His thrust must be to try and cure diseases of the metabolic syndrome through evolutionary medical care, not just to treat them. He must be willing to reduce medication where ever possible, and have a working knowledge of supplements that can be complimentary in that endeavor. Please believe that some metabolic syndrome diseases can be halted or reversed, and in some cases even cured.

Case in point, 12 months ago, I started an evolutionary life style under the advice and evolutionary health care of Dr. Tourgeman, A.K.A the dedicated evolutionary health care practitioner, Dr. T. The following is a partial list of ailments that I had accrued: Incurable Chronic Kidney Disease, Diabetes type 2, Poor lipids, painful Arthritis in hands and feet, and obesity to mention just a few. How did I get here you might ask? I followed the advice of the doctors that were treating me at that time and I read many books, over 22 to be exact. What the doctors were preaching and all the many books had in common was that they all were based on the so called wrong healthy eating dogma, of low saturated fat and high carbohydrate with nary a mention of vitamin D3 or fish oil. At that time in my life I never heard of an evolutionary life style. Very few people did. I kept following the advice of my doctors and kept on reading all the wrong books. Ultimately I became ill with diabetes type 2 which according to my current doctor led me to chronic kidney disease. Well, that was then, and thankfully this is now. My report card so far in just 12 months: CKD halted and some markers reversed, Diabetes type 2 cured, Lipids almost perfect, and my high LDL number is being treated with a niacin supplement, all arthritic pain abated in my hands and feet, and a weight loss of 55 pounds and falling. Any doctor would be proud with being able to accomplish this magnificent feat. How did Dr. T do it? He gave me information about the evolutionary life style and took me off statin drugs. He suggested, that I as his patient, switch from a low saturated fat diet with a high carbohydrate content to a high saturated fat and low carbohydrate program, along with a high vitamin D3 and high fish oil content. He is truly a physician who practices evolutionary medicine. In my opinion, and with these results, this is the only medicine worth practicing.

If you think that this sounds like a lot to expect from your doctor, it is. After all, most doctors believe only what they were taught in medical school or have had passed on to them from other medical colleagues. They certainly did not learn about an evolutionary life style as being the optimum lifestyle that our genes require for good health. I don’t blame them for resisting this information, they were taught to promote a low fat and a high carbohydrate lifestyle. Most of the research out there is keyed toward this wrong dogma. Did you ever ask why this is so? Big pharma pays for most of the clinical research that is being done. If you look at the end of any clinical study, it invariably tells you who sponsored the study. It is a real eye opener. Big Pharma is always hoping to cash in by inventing a pill that will alleviate the symptoms of the disease that they are sponsoring the clinical trials for. If it weren’t so sad it would be comical. A case in point is Statin drugs. Most doctors prescribe a Statin, and indeed many take them themselves. You see, they bought in to the hype of big Pharma. I have a doctor who takes Statin drugs him self. When he found out that with the advice of another doctor, I stopped taking them, he was outraged. I calmed him down as best I could, and asked him to order a VAP lipid panel for me, which he did. Three months later he ordered another lipid panel and made a comparison with the previous one. He was stunned at the improvement in my lipids. A vast improvement without any Statin drugs what so ever. I shot for a lipid value of 60/60/60. My HDL is now 63mg/dl, TRIG is now 63mg/dl, but, my LDL was 153mg/dl, on the face of it a troubling number. But, when you consider that my lipid pattern size was mostly large and buoyant, I had very little to worry about. Because only small dense lipoprotein are the troubling lipoprotein that can penetrate a damaged artery wall, to adhere to that artery wall and cause plaque build up. Needless to say my primary doctor is coming around and getting comfortable with evolutionary medicine.

Other reasons that many doctors shy away from recommending an evolutionary life style are: fear of being sued, or ridiculed, or even loss of income. After all, who would cure people if it means that you will lose a customer? Some doctors just don’t have the time to learn new methods. Think about it. They spend about 15 minutes with a patient and they have a full schedule. I recently had one doctor who told me he would rather perfect his golf swing than put in the time studying new approaches. Yet, there are some doctors who are different. It is your job to seek out and find such doctors, who will at a minimum, be willing to monitor you while you are going through the transition from an unhealthy lifestyle to a health supporting one.

You know the old adage; a patient who is his own doctor has a fool for a patient. Be smart and be cautious, the life you save might well be your own.

This is my wish to you for the New Year. Good luck and good health. It’s in your hands.

Billy E